Condensations of Carbonyl Compounds at the Methyl or a-Methylene Group of 6- or 4-Alkyl-3-cyano-2( 1) -pyridones through Dianions' Sandra Boatman, Thomas M. Harris, and Charles R. Hauser
Contribution f r o m the Chemistry Department, Duke Universit v. Durham, North Carolina. Received Ju-ly 6, 1965 Several tj'pes of condensations of carbonyl compounds at the methyl or methylene group of 6- or 4-alkyl-3cyano-2(l)-pyridones were effected through dianions, which were prepared by means of 2 molecular equiv. of potassium amide in liquid ammonia. The types of condensations realized were aroylation with methyl benzoate, acylation with ethyl oxalate, carbonyl addition with benzophenone or benzaldehyde, and conjugate addition with chalcone. One of the benzoyl derivatives was converted b y polyphosphoric acid to the corresponding amide and another to a dihydroxy-2,7-naphthyridine. The carbonyl addition products were dehydrated or converted to another derivative. Consideration is given to possible extensions of the method.
of 2 was probably neutralized in converting the monoanion of the condensation product to its dianion.3 Similarly, cyanopyridones 4 and 7 were converted to dianions 5 and 8, which were benzoylated in the presence of 1 molecular equiv. of potassium amide to give 6 and 9 in yields of 75 and 68%, respectively. In these cases, the monoanion of the condensation product apparently is converted to its dianion by the alkali amide. C B H ~ ~ ? :" . ; O N CH3 N H 5
4
-
co &; CHI
I
A recent paper2 has described alkylations at the methyl or &-methylene groups of 6- and 4-alkyl-3cyano-2( 1)-pyridones with alkyl halides. This novel mode of alkylation was effected through corresponding dianions, which were prepared by means of potassium amide in liquid ammonia. The present paper describes some examples of several other types of condensations at the 6- and 4methyl or -methylene groups of certain alkylcyanopyridones with carbonyl compounds. Aroylation and Acylation. Two 6-methyl- and one 4-methyl-3-cyano-2( 1)-pyridones were aroylated with methyl benzoate through dianions, which were prepared by means of 2 molecular equiv. of potassium amide in liquid ammonia. Thus, dianion 2, prepared from pyridone 1, was benzoylated to form 3 in 80% yield. This reaction was effected with 2 molecular equiv. of dianion 2 to one of methyl benzoate, as half
2
1
(1) This investigation was supported by Public Health Service Research Grant No. CA 04455-06 from the National Cancer Institute and by National Science Foundation Grant No. NSF G P 2274. (2) S. Boatman, T. M. Harris, and C. R. Hauser, J . Org. Chem., 30, 3593 (1965)..
5198
Journal ofthe American Chemical Society
87:22
6
CsHs N H 7
C6H5 N' 8
c6H5n
C6HbCOCH2 N H 6
CsHsCOCHz &h
N
C6H5
0
H 9
Structures 3, 6, and 9 were supported by absorption spectra (see Tables I and 11). Their infrared spectra (KBr pellet) showed bands for the ketone carbonyl group, although this band in the spectrum of 6 appeared to be masked by that of the amide group carbonyl. Their ultraviolet spectra (in ethanol) exhibited maxima near the visible region, which might be attributed to enolized structures present in ethanolic solution; the two maxima characteristic of cyanopyridones were also observed. The n.m.r. spectrum of each compound (in trifluoroacetic acid) showed a singlet for the two methylene hydrogens. The singlets in the spectra of 3 and 6 were further downfield than that in the spectrum of 9 (see Table 11). This may be due to the electronwithdrawing effect of the ring nitrogen. However, the methylene of 9 appeared abnormally far upfield. It should be noted that the three types of spectra, obtained in different media, probably represent three different structures for each compound. Also, dianion 2 was acylated with ethyl oxalate by the second procedure mentioned above to afford 10 in 46% yield, Structure 10 was supported by absorption spectra. Its infrared spectrum showed absorption bands for the ester, ring-amide, and nitrile groups at 5.80, 6.05, and 4.46 p, respectively. Its ultraviolet spectrum exhibited maxima at 420 mp (log e 4.25), 294 (3.73), and 277 (3.81).
10
(3) See R. J. Light and C. R. Hauser, ibid., 25, 538 (1960). (4) See S. D. Work and C. R. Hauser, ibid., 28, 725 (1963).
1 November 20, 1965
Table I. Infrared and Ultraviolet Spectral Data for the Pyridones
Pyridone
Ring amide
6.03, 6.14,6.23 6.00, 6.15, 6.22 6.03, 6.25, 6.41 6.08,6.18,6.33 6.06 . . . . . . 6.05,6.21,6.36 6.00,6.28,6.41 6.08,6.27, . . . 6.00,6.18, 6.31 6.00, 6.16,6.31 6.08,6.20, 6.33 6.09,6.24,6.36 6.01,6.18,6.36 6.10,6.21,6.34 6.03, 6.22,6.31
3 6 9
10 13 14 15 17 18 19 20 21 22 26 5
Infrared spectrum, p Nitrile
Keto carbonyl.
b
Shoulder.
c
--
4.46 4.46
4.50
...
4.49 4.46 4.47 4.48
5.9Y 5.7gC 2.94d
...
...
4.48 4.48 4.52 4.50 4.49 4.55
2.92d 5.13c 2.86d
d
Amax mp
5.8ga 5,850
435, 338,242 448, 345,245 405,b359, 270 420,294,b 217 338, 235 338, 246, 237 354, 245 338, 236 380, 339, 235 351,246 385, 340,216 339, 242 356, 246, 226 351, 242
...
...
5.94 5.95" 5.93s
4.55
Ester carbonyl.
Ultraviolet spectrum
7
Other
Log
e
3.64,4.06,4.23 3.69, 4.04,4.38 3.76,4.22,4.25 4.25, 3.73, 3.81 4.12,4.04 4.28,4.32,4.30 4.18, 4.48 4.13, 3.92 3.38,4.07, 3.95 4.24,4.40 4.16,4.34,4.25 4.08,4.23 4.21,4.25, . . . 4.09,4.28
Hydroxyl group.
Table 11. N.m.r. Data for the Cyanopyridones ~~
Cyanopyridone
Type of hydrogen
3
21
I1
22
2(0.36) 2 (0.36)
Sharp peak with shoulders Singlet Singlet Complex group Singlet Doublet Several peaks Two complex groups
4.92 6.65,6.18 8.00, 8.13 I . 66-8.54 4.56 8.05 6.87-1.78 2.65 1.04, 7.13 7.23-8.14 2.94-4.30
2 (0.11) l(O.09) 10 (1 .O) 2 (0.20) l(0.12) 10 (1 .O) 4 (0.43)
Several peaks
6.45-8.18
12 (1.0)
Two complex groups Singlet Several peaks
3.16-4.06 6.90 7.23-8.23
Singlet Pair of doublets
Methylene 5 H of pyridone Phenyl Methylene 4 H of pyridone Phenyl CHICHCH~ 4 and 5 H of Dyridone Ph'hnyl CHICHCH~ 4 H of Dyridone Phenyl
9
No. of hydrogens (relative peak intensity)
Peak character
Methylene 4 and 5 H of pyridone Phenyl
6
Peak center or over-all range, p.p.m.
Treatment of benzoyl derivatives 3 and 9 with polyphosphoric acid produced amide 11 and cyclic product 12 in yields of 91 and 65 %, respectively. In the latter reaction, the corresponding amide was presumably an intermediate.
myH2
CeHsCOCHp N H 11
C6H5
5 (1 .O)
5 (0.33)
1 (0.06) 15 (1.0)
Carbonyl Addition. Dianion 2 (see preceding section) underwent an addition reaction with benzophenone to form 13 in 87% yield. Adduct 13 was dehydrated with acetic anhydride in the presence of a
aC&
13
12
Structures 11 and 12 were supported by absorption spectra. The infrared spectrum of 11 showed amide carbonyl absorption at 5.96 p and showed no nitrile band; a doublet for the hydrogens of NH2 was present at about 3.1 p. The ultraviolet spectrum exhibited maxima at 331 mF (log E 4.06) and 240 mp (log e 3.80). The infrared spectrum of 12 showed absorption at 6.10, 13.00, and 14.45 p ; no absorption characteristic of nitrile or hydrogens of an amide NH2 was observed. The ultraviolet spectrum exhibited maxima at 360 mp (log e 4.40)and 271 mp (log E 4.49). Boatman, Harris, Hauser
Condensations of Alkyl-3-cyano-2(l)-pyridones
5199
catalytic amount of concentrated sulfuric acid to give 14 in 99% yield. Product 14 was decyanated (probably through decarboxylation of the carboxylic acid) with refluxing 50 % sulfuric acid to afford 15, which was independently synthesized from 6-methyl-2(1)-pyridone through its dilithio salt 16.5 The structures of these products were further supported by absorption spectra. Their ultraviolet spectra showed the expected maxima near 338 and 235 mp for 13 and 14, and 245 mp for 14 and 15 (see Table I). The infrared spectrum of 13 showed an OH band which was missing in 14 and 15. The infrared spectra of 13 and 14 showed CN absorption near 4.48 p, which was missing in 15. Similarly dianion 2 underwent an addition reaction with benzaldehyde to form 17 in 67% yield. Acetylation of 17 to form 18 was accomplished with acetic anhydride and a catalytic amount of sulfuric acid. The infrared spectrum of 17 showed an OH band at 2.92 p, and that of 18 showed an ester peak at 5.73 p , The ultraviolet spectra of both gave the expected maxima and extinction coefficients (see Table I).
00 \
CsH5CHCH2G
I
O
CsH5CHCH2
I
OH
18
Likewise dianion 8 (see previous section) underwent an addition reaction with benzophenone to give 19 in 80% yield; 19 was dehydrated with concentrated sulfuric acid to afford 20 in 91 % yield. The structures were supported by infrared and ultraviolet spectra (see Table I). OH
I
3Tic
(C6H5)2
& w 6 2 -
c6HS N
C6H5
H
N H
19
20
Conjugate Addition. Dianions 2 and 8 (see aroylation section) underwent conjugate addition with chalcone to form 21 and 22 in yields of 87 and 86%, respectively. 1.CeH,CH=CHCOCeHs
'
2.acid
H5C< C a H ~ f l O g C6H5COCH2CHCH2 N H
21
22
23
Structures 21 and 22 were supported by absorption spectra. Their infrared spectra showed bands for the ketone carbonyl group (see Table I), and their n.m.r. spectra exhibited complex peaks for one methinyl and four methylene hydrogens (see Table 11). Their ultraviolet spectra showed the expected maxima and ( 5 ) This salt was prepared by means of two molecular equivalents of n-butyllithium in tetrahydrofuran; the details of this new method will be published soon.
5200
Journal of the American Chemical Society
I CGHS 24
25
26
Structure 26 was supported by infrared and ultraviolet spectra (see Table I), and by independent synthesis from dianion 27 as described recently.6
-bo 0
1. CeH&H=CHCOC& 2. NCCHzCONHz
+
26
CN
OCOCH:, 17
extinction coefficients (see Table I). That the products were not the possible carbonyl addition adducts, for example 23, was further indicated by the absence of a hydroxyl band in the infrared spectra, and by failure to undergo dehydration with cold, concentrated sulfuric acid. Similarly pyridone 24 was converted to dianion 25, which was condensed with chalcone to give 26 in 65% yield.
87:22
27
Discussion The scope of the carbonyl condensations illustrated above could presumably be extended considerably. Thus, not only should other 4- and 6-alkyl-3-cyano-2( 1)pyridones undergo such reactions, but other aromatic esters, aromatic ketones or aldehydes, and a,punsaturated carbonyl or related compounds should also be suitable for aroylations, carbonyl additions, and conjugate additions, respectively. Extensions of the method to aliphatic esters and ketones seems possible by the use of dilithio salts of the cyano pyridones. As pointed out previously,2 pyridones having an activating group other than C N might also be suitable for such condensations. Experimental Section' Pyridone Dianions. The starting cyanopyridones 1, 4, 7, and 24 were prepared as reported previously.2 In a typical experiment, 0.05 mole of the pyridone was added to 0.108 mole of potassium amide, prepared from 0.108 g.-atom of potassium in commercial, anhydrous, liquid ammonia.* Conversion to the dianion was assumed to be complete after the solution had stirred for 1 hr. Dianions 2 and 5 were red, and 8 and 25 were green. Benzoylations. A . Of 6-Methyl-3-cyano-2(1)-pyridone Dianion (2) to Form 3. To a stirred solution of 0.118 mole of dianion 2 in 700 ml. of liquid ammonia was added 8.0 g. (0.059 mole) of methyl benzoate in (6) T. M. Harris, S. Boatman, and C. R. Hauser, J . Am. Chem. SOC., 87, 3186 (1965). (7) Melting points were taken on a Mel-Temp capillary melting point apparatus and are uncorrected. Infrared spectra were determined with Perkin-Elmer Infracords, Models 137 and 237, with potassium bromide pellets or Nujol mulls. N.m.r. spectra were obtained with a Varian A-60 spectrometer using trifluoroacetic acid as solvent and tetramethylsilane as an external reference. Ultraviolet spectra were obtained with a Cary Model 14 spectrometer using solutions approximately IO-' M in 95 % ethanol. Elemental analyses were by Galbraith Laboratories, Knoxville, Tenn., Triangle Chemical Laboratories, Chapel Hill, N. C,, and Janssen Pharmaceutica, Beerse, Belgium. (8) See C. R. Hauser and T. M. Harris, J . Am. Chem. SOC.,80, 6360 (19 58).
/ November 20, 1965
ether. The mixture was stirred for 40 min. before neutralization with ammonium chloride. The ammonia was evaporated, and the mixture was washed with dilute hydrochloric acid and filtered. The precipitate was washed with water and then stirred briefly with a solution of 6 g. of sodium hydroxide in 50 ml. of water. The remaining solid was collected and washed with water. Acidification of the combined washings and alkaline solution afforded 11.2 g. (80%) of the pale yellow 6-phenacyl-3-cyano-2( 1)-pyridone (3), map. 199-205 ". Recrystallization from ethanol gave two crystalline forms: on fast cooling, white needles, m.p. 209-21 1', and on slow cooling, yellow rhomboids, m.p. 210-212". Although their infrared spectra were slightly different (see Table I), their mixture melting point was undepressed. Anal. Calcd. for Cl4H1oNz02: C , 70.58; H, 4.23; N, 11.76. Found: C, 70.71; H, 4.24; N, 11.84. A 2-g. sample of 3 was heated with 20 g. of polyphosphoric acid at 150" for 1 hr. The solution was diluted with 150 g. of ice, and the resulting mixture was filtered. The solid was washed with saturated sodium bicarbonate solution and water and recrystallized from ethanol to give 1.9 g. (91 %) of 6-phenacyl2( l)-pyridone-3-carboxamide( l l ) , m.p. 287-289 '. Anal. Calcd. for CI4Hl2N2O3: C, 65.52; H, 4.72; N, 10.93. Found: C, 65.70; H, 4.73; N, 10.92. B. Of 6-Methyl-5-phenyl-3-cyano-2(1)-pyridoneDianion (5) to Form 6. To a stirred solution of 0.05 mole of dianion 5 and an additional 0.06 mole of potassium amide (prepared from 0.06 mole of pyridone 4 and 0.15 mole of potassium amide) in 800 ml. of liquid ammonia was added 8.2 g. (0.06 mole) of methyl benzoate in 20 ml. of ether. The ammonia was allowed to e ~ a p o r a t e ,and ~ the residue was dissolved in ether and cold water. The two layers were separated. The aqueous layer was acidified with 6 M hydrochloric acid. The solid was collected, washed with water, and recrystallized from ethanol (solution was deep yellow) to afford a mixture of pale yellow needles and orange platelets, m.p. 237-245 '. Further recrystallization from ethanol afforded 4.9 g. (78%) of 6phenacyl-5-phenyl-3-cyano-2( 1)-pyridone (6), m.p. 247248 ". Anal. Calcd. for CzoH14N~O~: C, 76.42; H, 4.49; N, 8.91. Found: C, 76.43; H, 4.42; N, 8.80. C. O f 4-Methyl-6-phenyl-3-cyano-2(1)-pyridoneDianion (8) to Form 9. The reaction was carried out as in B, using 0.05 mole of dianion 8. One recrystallization of the product from ethanol afforded 10.3 g. (65 %) of 4-phenacyl-6-phenyl-3-cyano-2(1)-pyridone (9), m.p. 248-250'. Anal. Calcd. for C20H14N202: C, 76.42; H, 4.49; N, 8.91. Found: C, 76.19; H, 4.43; N, 8.93. A 2-g. sample of 9 was heated with 20 g. of polyphosphoric acid at 150' for 1 hr. The solution was diluted with 150 g. of ice, and the resulting mixture was filtered. The solid was washed with saturated sodium bicarbonate solution and water and recrystallized from glacial acetic acid to give 1.2 g. (65 %) of 1,8dihydroxy-3,6-diphenyl-2,7-naphthyridine(12), m.p. 296-297 ". (9) This procedure, which is used also in (C), differs from that in (A), because the products of (B) and (C) could not be separated from their respective starting materials by stirring the mixture with aqueous base of varied concentrations.
Anal. Calcd. for C20H14N202: C, 76.42; H, 4.49; N, 8.91. Found: C, 76.50; H, 4.58; N, 8.65. Acylation of Dianion 2 with Ethyl Oxalate. The reaction was carried out as in B above using 0.05 mole of dianion 2, except that the ammonia was replaced by anhydrous ether, which was distilled and replaced until there was no detectable ammonia odor. A solution of 11.0 g. (0.075 mole) of ethyl oxalate in ether was added, and the mixture was refluxed for 8 hr. The work-up was carried out as in B. The product 10 was obtained in 46% yield (4.8 g.), m.p. 237-235" after recrystallization from ethanol. Compound 10 gave a green color with alcoholic ferric chloride. Anal. Calcd. for C I I H I O N ~ O ~C:, 56.41; H, 4.30; N, 11.96. Found: C, 56.34; H, 4.31; N, 11.92. Carbonyl Additions. A . Of Dianion 2 with Benzophenone to Form 13. To a stirred solution of 0.025 mole of dianion 2 in 500 ml. of liquid ammonia was added 7.10 g. (0.039 mole) of benzophenone in ether. After 15 min. the green slurry was poured into a mixture of 5 g. of ammonium chloride and 200 ml. of liquid ammonia. The ammonia was evaporated and the residue was suspended in water. The mixture was filtered. The solid was washed with water and a little ether and dried to afford 6.9 g. (87%) of adduct 6-(2,2diphenyl-2-hydroxyethyl)-3-cyano-2( 1)-pyridone (13), m.p. 208-210'. Recrystallization from ethanol raised the melting point to 215-216". Anal. Calcd. for CzoH1eNzO2: C, 76.06; H, 5.07; N, 8.81. Found: C, 76.00; H, 5.12; N, 8.94. Dehydration was effected by heating 3.0 g. of 13 with 20 ml. of acetic anhydride and about 0.1 ml. of sulfuric acid on the steam bath for 2 hr. Sodium carbonate (0.1 8.) was added, and the mixture was poured into water. After the acetic anhydride had been hydrolyzed, the precipitate was collected and dried to give 2.7 g. (99%) of 6-(2,2-diphenylvinyl)-3cyano-2(1)-pyridone (14), m.p. 241-243 O and 242.5244' after recrystallization from ethanol. Anal. Calcd. for C20H14N20: C, 80.51; H, 4.73; N, 9.39. Found: C, 80.46; H, 4.93; N, 9.48. Decyanation was effected by heating 3.9 g. of 14 in a solution of 12 ml. of sulfuric acid and 12 ml. of water at 150' for 10 hr. The mixture was cooled and poured over ice. The precipitate was collected and was recrystallized from ethanol to afford 3.0 g. (84%) of 6-(2,2-diphenylvinyl)-2( 1)-pyridone (15), m.p. 206209" (21 1-213 ' after further recrystallization). Anal. Calcd. for C19H15NO: C, 83.49; H, 5.53; N, 5.13. Found: C, 83.59; H, 5.58; N, 4.90. Independent synthesis of 15 was accomplished by dehydration of the condensation product of benzophenone and dilithio-6-methyl-2(l)-pyridone (16).6 Samples of 15 prepared by the two routes were shown to be identical by mixture melting point and infrared spectra. B. Of Dianion 2 with Benzaldehyde to Form 17. To a stirred solution of 0.025 mole of dianion 2 in 500 ml. of liquid ammonia was added 5.3 g. (0.05 mole) of benzaldehyde. The red color became dark green and then gradually brown. After 10 min., the solution was poured into a mixture of 6 g. of am-
Boatman, Harris, Hauser / Condensations of Atkyl-3-cyano-2(1)-pyridones
5201
monium chloride and 100 ml. of liquid ammonia. After evaporation of the ammonia, the sticky residue was filtered and washed with cold water. Crystallization from ethanol afforded 4.0 g. (67 %) of 6-(2-phenyl2-hydroxyethyl)-3-cyano-2(1)-pyridone (17), m.p. 195-196" (205-206" after recrystallization from ethanol). Anal. Calcd. for C14H1zNzO2: C, 70.47; H, 4.95; N, 11.47. Found: C, 70.50; H, 5.03; N, 11.65. Acetylation was accomplished by dissolving 1.9 g. of 17 in 10 ml. of acetic anhydride and 1 drop of sulfuric acid. The mixture was warmed on the steam bath to effect solution and then allowed to stand at room temperature for 8 hr. A small amount of potassium carbonate was added, and the acetic anhydride and acetic acid were removed under reduced pressure. The residue was taken up in ethyl acetate, and the solution was filtered and evaporated. Recrystallization of the residue from ethanol afforded 1.75 g. (78 %) of acetylation product 18, which momentarily melted and then resolidified at about 200" and then melted again at 308-310" dec. The first transition may have reflected loss of acetic acid or the occurrence of some other chemical transformation. Anal. Calcd. for C l s H ~ ~ N 2 0 sC,: 68.07; H, 5.00; N, 9.93. Found: C, 68.28; H, 4.95; N, 10.02. C. Of Dianion 8 with Benzophenone to Form 19. This reaction was carried out as in part A of this section, using 0.05 mole of dianion 8, 9.1 g. (0.05 mole) of benzophenone, and 10 g. of ammonium chloride. Recrystallization of the product from ethanol afforded 15.8 g. (80 %) of 4-(2,2-diphenyl-2-hydroxethyl)-6phenyl-3-cyano-2( 1)-pyridone (19), m.p. 240-242 ". Further recrystallization raised the melting point to 250-25 1.5". Anal. Calcd. for CZ~HZONZOZ: C, 79.57; H, 5.14; N, 7.14. Found: C, 79.87; H, 5.18; N, 7.14. Dehydration was accomplished by dissolving 2.5 g. of 19 in 25 ml. of concentrated sulfuric acid at about 5 ", and then pouring the solution over 100 g. of ice. The resulting solid was collected, washed with sodium carbonate solution, and water, and recrystallized from ethanol to afford 2.0 g. (91 %) of 4-(2,2-diphenylvinyl)-6-phenyl-3-cyano-2(1)-pyridone (20), m.p.
272-274". Further recrystallization raised the melting point to 275-276". Anal. Calcd. for CzeH18Nz0: C, 83.40; H, 4.85; N, 7.48. Found: C, 83.47; H, 4.86; N, 7.60. Conjugate Additions. A . Of Dianion 2 to Form 21. To a stirred solution of 0.05 mole of dianion 2 in 700 ml. of liquid ammonia was added 11.0 g. (0.105 mole) of chalcone. After 1 hr. the ammonia was evaporated, and the residue was dissolved in ether, ice, and water. The aqueous layer was separated and acidified with 6 M hydrochloric acid. The resulting precipitate was collected, washed with water, and recrystallized from ethanol to afford 14.9 g. (87%) of 6-(2,4-diphenyl-4oxobutyl)-3-cyano-2( 1)-pyridone (21), m.p. 216-222 O (227-228 " after recrystallization from ethanol). Anal. Calcd. for Cz2Hl8N2OZ:C, 77.17; H, 5.30; N, 8.18. Found: C,77.04; H, 5.11; N, 8.34. A sample of 21 was recovered unchanged after treatment with cold, concentrated sulfuric acid. B. Of Dianion 8 to Form 22. This reaction was carried out as in part A of this section, using 0.05 mole of dianion 8. Recrystallization of the product from ethanol afforded 18.0 g. (86%) of 4-(2,4-diphenyl4-oxobutyl)-6-phenyl-3-cyano-2( 1)-pyridone (22), m.p. 252-255 " ; further recrystallization raised the melting point to 261.5-262". Anal. Calcd. for C28HzzN20z:C, 80.36; H, 5.29; N, 6.69. Found: C, 80.58; H; 5.33; N, 6.50. This product was unchanged by treatment with cold, concentrated sulfuric acid. C . Of Dianion 25 to Form 26. This reaction was carried out as in part A of this section, using 0.05 mole of dianion 25. Recrystallization of the product from glacial acetic acid afforded 12.4 g. (65%) of 1,2,5,6,7,&hexahydro- 3 -cyano - 8-( 1,3-diphenyl- 3 -oxopropyl)-2-quinolone (26), m.p. 259-260" (lit.6 m.p. 261-263"). Independent synthesis of 26 was accomplished by addition of chalcone to the dianion of 2-formylcyclohexanone, followed by cyclization with cyanoacetamide. The identity of samples of 26 obtained by the two routes was established by mixture melting point and by infrared spectra.
The Kinetics of the Permanganate Oxidation of Acetone' Kenneth B. Wiberg and Richard D. Geer
Contribution f r o m the Departments of Chemistry, Yale University, New Haven, Connecticut, and the University of Washington, Seattle, Washington. Received M a y 7, 1965 The kinetics of the permanganate oxidation of acetone were examined in basic aqueous solution. The data suggest that the enolate ion is an intermediate, and that it is oxidized by permanganate via an electron transfer rather than addition to the double bond. The rates of oxidation of the possible intermediates, and the products (1) This work was supported by the U. S. Atomic Energy Comrnission.
5202
of the oxidation were determined. The data indicate the nature of the reactions which occur.
One of the most common modes of oxidation of aliphatic aldehydes and ketones involves reaction a t the a-position.2 Our interest in the general subject of (2) Cf.J. S. Littler, J . Chem. Soc., 827, 832 (1962).
Journal of the American Chemical Society / 87:22 / November 20, 1965
